9-12 November 2003, Braunschweig, Germany
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Development and Stem Cells *
Functional Genome Analysis *
Mouse Models of Human Disease *
Mouse System Biology Bioinformatics *
Multigenic and Multifactorial Trait Analysis *
Nutrition and Metabolic Disease *
Phenotyping Methods Imaging *
The Genetics and Genomics of Infectious Disease *
Verne Chapman Memorial Lecture
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POSTER 39 - IDENTIFICATION OF TUMOUR-ASSOCIATED GENES IN THE PROCESS OF MURINE SKIN CARCINOGENESIS
Hummerich L
Division of Molecular Genetics
Co-Authors: 2) Müller R, 1) Wrobel G, 1) Kokocinski F,
2) Gack S, 2) Schorpp-Kistner M, 3) Fürstenberger G, 2)
Hess J, 1) Hahn M, 2) Angel P, 1) Lichter P
Institutions: 1) Division of Molecular Genetics, 2) Division
of Signal Transduction and Growth Control, 3) Division
Biochemistry of Tissue-Specific Regulation, Deutsches
Krebsforschungs-zentrum, Im Neuenheimer Feld 280, D-69120
Heidelberg, Germany
The mouse skin models of chemical carcinogenesis have
been extensively used to investigate skin tumour initiation and
promotion and the conversion of benign tumours (papillomas) to
malignant squamous cell carcinomas (SCC). To provide reliable
diagnostic markers and to develop novel therapeutic targets for
cancer prevention and treatment, an understanding of the
molecular basis of tumourigenesis will be essential.
Particularly, identification and functional characterization of
cellular genes that are targeted by oncogenic stimuli
represents an auspicious experimental approach. For the studies
of skin cancer modulation 7,12-dimethylbenzanthracene
(DMBA)-initiated and 12-O-tetradecanoyl-phorbol-13-acetate
(TPA)-promoted back skin of mice are used to identify
tumour-associated genes in the steps of initiation, promotion
and progression. The different RNA samples derived from control
and short-term TPA-treated skin, papilloma and SCC biopsies
were hybridised on two different arrays comprising 20K (LION
arrayTAG™) and 15K (National Institute of Aging)
murine gene specific cDNA fragments. Expression data of
selected genes were confirmed by semiquantitative RT-PCR,
quantitative real-time PCR (RQ-PCR) and in situ
hybridisation (ISH). Besides numerous known genes, we
identified a large set of unknown cDNAs representing previously
unrecognised TPA-regulated genes in murine skin with potential
function in tumour promotion. The detailed analysis of genes,
involved in the development of papillomas and in the conversion
of papillomas to malignant squamous cell carcinomas, might
identify potential candidates for a better understanding of the
molecular mechanism of skin carcinogenesis.
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